The knock‐down of Caveolin‐1 inhibits STAT3 signaling in human metastatic lung cancer in vitro

Abstract

Caveolin‐1 (Cav‐1) is an essential structural constituent of caveolae, implicated in mitogenic signaling, oncogenesis, neurodegenerative diseases and senescence. A complex role is exerted by Cav‐1 in human malignancies, which seems to be dependent on histotype, stage and grade of each neoplastic disease. As regards lung cancer, emerging evidence indicates a close relation between Cav‐1 and the development of it. In the present study we investigated the role of Cav‐1 in metastatic lung cancer proliferation. Cell lines were from metastatic lesions of lung adenocarcinoma (RAL) and of small cell lung carcinoma (SCLC‐R1), in which Cav‐1 protein was expressed at high levels. Results show that siRNA‐mediated down‐regulation of Cav‐1 caused stable arrest of cell cycle in both cell lines. A marked reduction of cyclin D and of CDK2‐CDK4 expressions were evident in the cells transfected with Cav‐1 siRNA and consequently of phosphoRb on ser795 and ser780. A significant decrease of the expression of phosphorylated Akt and its down‐stream effectors phosphorylated ERK and STAT3 was also evident. This is the first report of a block of metastatic lung proliferation obtained by Cav‐1 silencing, in the same time suggesting a new cell cycle inhibiting pathway, mediated by Cav‐1 knock‐down, in lung cancer and providing new insights into the molecular mechanism underlying the pro‐survival and tumor‐promoting functions of Cav‐1Grants from MIUR (RFO, PRIN), Pallotti's Legacy for Cancer Research, University of Bologna, Italy